CLINICAL TRIALS
becomes more complex, and that the costs of concerned that everything would have a and communication of the risks of medicines
drug development increase. REMS.” In fact, she observed, what the agency throughout their life cycle.
Companies will also need to act quickly had required so far had been “probably very Among the aims of the programme are to
if new safety signals emerge for one of their
similar to the pace we would have been on if make the EudraVigilance system more fully
products: the FDA can now ask a fi rm to
we’d not had these authorities, and it’s simply functional, improve the workings of the EU
submit a REMS for an approved drug within
that these are [now] required by the FDA.”
regulatory system network, and implement
four months.
the European Network of Centres for
For its part, the FDA has many more
Europe’s initiatives
Pharmacoepidemiology and Pharmacovigilance
Efforts are also under way across the Atlantic
responsibilities in terms of ensuring safety
(ENCePP) project.
to implement a more proactive approach to
and minimising risk. For example, it now
The EU has other plans in store to strengthen
managing product risks. Under EU legislation,
has to integrate the REMS not only into
drug safety monitoring, in the form of a directive
companies have to provide risk management
the drug approval process but also in the
drafted by the European Commission. The
plans (RMPs) with new product applications
post-marketing phase. In fact, the agency can
commission had planned to unveil the document
and extensions, as well as at the request
mandate a REMS at any point in the product’s
on October 21st as part of a “pharmaceutical
of the authorities and when new relevant
life cycle if fresh safety information arises from,
package” that also contained draft legislation on
safety data emerge. RMPs consist of a safety
say, clinical trials, adverse event reporting or
anti-counterfeiting measures and information
specifi cation and a pharmacovigilance plan
post-marketing studies. To support its decision-
to patients, although in the event its publication
and, where appropriate, a risk minimisation
making, the FDA will set up an active risk
was postponed. The pharmacovigilance directive
plan.
identifi cation network with a master database,
was expected to put forward a range of ideas
Existing RMPs can be modifi ed if new
using data obtained from a wide range of
safety information comes to light. One recent
for reinforcing and rationalising decision-making
sources.
example of this was Biogen Idec/Elan’s Tysabri
on safety issues. Many of the proposals will
The FDAAA also brings new requirements
(natalizumab) for multiple sclerosis. In July
bring new obligations for both regulators and
in the area of paediatric medicines. Previously,
2008, the EMEA received two reports of
companies.
only products granted exclusivity under the progressive multifocal leukoencephalopathy
They could include stronger obligations on
Best Pharmaceuticals for Children Act had (PML) in patients with relapsing-remitting MS
companies to notify regulators of any changes to
to undergo a one-year post-exclusivity safety taking Tysabri. The two cases were reported
their products’ risk-benefi t profi le, including new
review. But now such reviews will be triggered
information from clinical studies; giving regulatory
when data from studies requested by the
authorities more power to request post-
agency under the Pediatric Research Equity Act
The FDA’s increased powers
authorisation safety studies; and an automatic
are added to product labelling. This will mean
pharmacovigilance referral procedure triggered
could result in products
a signifi cant increase in the number of reviews,
by events such as inspections.
with up to 40 products expected to be subject
with safety concerns being Other proposals in the directive could
to review in 2009, compared with 70 in the approved on condition that
include obliging member states to enforce
period from late 2003 to 2007.
penalties when companies fail to comply with
the manufacturer puts in place
To help it to meet its new responsibilities,
pharmacovigilance provisions, and introducing
the FDA has had to take on more scientifi c
a REMS or conducts post-
intensive monitoring for new products.
The delay to the “pharmaceutical package”
and administrative staff. By October 2008 it
authorisation studies
disappointed the pharmaceutical industry
was hoping to have added a total of 1,300
federation EFPIA, which said it was an “integral
personnel.
Nonetheless, there have been suggestions
as part of the continuous safety monitoring of
part of the process of ensuring and securing the
that the increase in the agency’s workload
medicines following marketing authorisation. supply of safe, non-counterfeit medicines and
The EMEA’s scientifi c committee, the to improve health literacy among patients”. It
will inevitably affect its ability to conduct
CHMP, launched a review of Tysabri to is not clear what caused the hold-up, although
its other activities. The result could be a
determine whether any changes to the it is likely to be due to one of the other two,
slowdown in the drug approval process or
approved product information or the existing more controversial, documents on patient
a fall in the number of meetings it can hold
risk minimisation measures were needed. In information and counterfeiting, rather than the
with companies. In fact, in August 2008 the
September the committee said the existing pharmacovigilance proposals.
FDA reported that action on some drug and
warning on the risk of PML should be There has been speculation that elements
biological applications had indeed been delayed
strengthened, and asked for an update of of the proposals on patient information are
beyond user fee deadlines while staff worked
the “Physician Information and Management
still being argued over within the commission’s
through the new drug safety requirements,
Guidelines for Multiple Sclerosis Patients on
services. The commission said the package would
including complex REMS proposals.
Tysabri”. These guidelines are part of the
be made public on November 26th, but declined
Conversely, some believe that the FDAAA
agreed RMP for the product, and set out a
to give any explanation for the delay, citing
could actually help some delayed drugs get
series of risk minimisation measures.
only “technical questions” that needed to be
to market. The FDA’s increased powers could
On a wider scale, the EU authorities
addressed. But the package was then postponed
result in products with safety concerns being
are taking steps to strengthen the entire
again, this time for “agenda reasons”. At the time
approved on condition that the manufacturer
pharmacovigilance system. At the end of
of writing industry sources were expecting it
puts in place a REMS or conducts post- 2007, the EMEA and the heads of national
some time during December.
authorisation studies. medicines agencies (HMA) agreed on a rolling
And by November it appeared that the FDA two-year (2008-2009) work programme
was applying the FDAAA in a fairly measured to further develop the European Risk
manner, and that the fl ood of requirements Management Strategy. The ERMS is intended
Ian Schofi eld is a principal
analyst for Informa Pharma.
some had predicted had not materialised. Janet
to allow pharmacovigilance activities to be
Woodcock, director of the agency’s drugs
conducted in a more proactive manner by
centre, told the DIA/FDA/PhRMA drug safety
putting in place measures that allow for the
conference in Virginia: “Everybody was very
early detection, assessment, minimisation
74
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